【作者】 冯强； 于敏之； 侯文杰； 王坚成； 张强；

【Author】 FENG Qiang;YU Min-zhi;Hou Wen-jie;WANG Jian-cheng;ZHANG Qiang;Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University;

【机构】 北京大学药学院药剂学系；

【摘要】 目的构建伐普肽表面修饰的核壳型纳米粒,共同递送紫杉醇与siRNA,并利用伐普肽介导的主动靶向效应增强siRNA与PTX的生物学效应。方法本实验首先通过保护-脱除的策略合成了导向化合物DSPE-PEG-VAP,再通过层层自组装的方法构建了靶向共递送系统VAP-PLPC/siRNA。通过粒径、电位、体外释放以及血清存在条件下对siRNA的保护效应等指标对载体的性质进行了初步评价。通过流式细胞术和激光共聚焦显微镜研究了纳米粒的细胞摄取情况。通过SRB法评价了制剂的体外肿瘤抑制效应。通过ELISA法测定了纳米粒对VEGF的沉默效应。结果该核壳结构纳米粒对siRNA具有良好的保护效应,使紫杉醇具有缓释性质。靶向配体修饰有利于siRNA和PTX药效的发挥。结论伐普肽修饰的核壳结构纳米粒是一种有效的PTX和siRNA共递送系统。更多还原

【Abstract】 OBJECTIVE To construct the core-shell type nanoparticles with vapreotide surface modification for the co-delivery of PTX and siRNA,and enhance the biological effects of PTX and siRNA by vapreotide.METHODS DSPE-PEG-VAP was firstly synthesised via a protecting-deprotecting strategy.Then,the nanoparticles were obtained by a layer-by-layer method.The physical properties of the nanoparticles were evaluated by measuring the size,zeta potential,PTX release rate and protection efficacy of siRNA against FBS.Cellular uptake of the nanoparticles were measured by FCM and CLSM.Cytotoxicity of PTX were evaluated in MCF-7 cells by SRB assay.In vitro gene silencing effects against VEGF of the nanoparticles were measured by ELISA.RESULTS The siRNA in nanoparticles were well protected against FBS and PTX showed a lower release rate than Taxol.Surface modification of vapreotide enhanced the biological effects of the siRNA and PTX.CONCLUSION The vapreotide modified core-shell type nanoparticle is a robust co-delivery system for PTX and siRNA.更多还原